Endocannabinoid interference blocks post-global cerebral ischemia depression through prefrontal cortico-amygdala projections

doi:10.1038/s41386-024-02029-4

	Endocannabinoid interference blocks post-global cerebral ischemia depression through prefrontal cortico-amygdala projections
	Tu, Zhaoyuan 1,2; Ma, Yao 1,2; Shang, Huiping 3; Zhao, Sha 4; Xue, Bao 4; Qu, Yu 4; Chen, Jiangfan 5,6; Li, Yulong 7; Hu, Ji8 ; Gao, Fang 9; Xu, Huamin 4,10; Xu, Xufeng 4,10; Zhang, Xia 1,2,3,4
	2024-11-01
发表期刊	NEUROPSYCHOPHARMACOLOGY (IF:6.6[JCR-2023],7.3[5-Year])
ISSN	0893-133X
EISSN	1740-634X
发表状态	已发表
DOI	10.1038/s41386-024-02029-4
摘要	Up to 45% of patients surviving from transient global cerebral ischemia (GCI) after cardiac arrest develop post-global cerebral ischemia depression (PGCID), but how to treat PGCID is clinically unknown. Here we find that cannabinoid type-1 receptor (CB1R) antagonists, CB1R knockout and endocannabinoid (eCB) synthesis inhibition block acute stress-induced PGCID. Application of acute stress to GCI mice increases CB1R activity from ventromedial prefrontal cortical (vmPFC) terminals synapsing with the basolateral amygdala (BLA) neurons, indicating the involvement of increased vmPFC-BLA synaptic eCB signaling in PGCID induction. This idea is supported by findings that optogenetic activation of CB1Rs in vmPFC-BLA projections mimics stress effects to induce PGCID, which is blocked by knock-down of eCB biosynthesis enzyme genes in vmPFC-BLA synapses. Interestingly, GCI mice show decreased mRNA expression of eCB degradation enzymes in vmPFCs without significant changes on mRNA expression of eCB biosynthesis and degradation enzymes in BLA cells. Thus, over-expression of eCB degradation enzymes in vmPFC cells innervating BLA neurons or activation of vmPFC-BLA projections blocks stress effects to induce PGCID. Our findings suggest that decreased eCB degradation and subsequent stress-increased eCB signaling in vmPFC-BLA circuits participate in the mechanism of PGCID, which can be treated clinically by eCB signaling interference systemically or in vmPFC-BLA circuits.
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收录类别	SCI
语种	英语
资助项目	Major program of Technological innovation 2030 "Brain science and brain- inspired research"[2021ZD0203002] ; National Natural Science Foundation of China["81830035","32371187","32000788"] ; Major program of National Natural Science Foundation of China[82090033] ; Major Basic research program of Shandong Province Natural Science Foundation[ZR2019ZD35] ; Natural Science Foundation of Shandong Province[ZR2024MH063]
WOS研究方向	Neurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry
WOS类目	Neurosciences ; Pharmacology & Pharmacy ; Psychiatry
WOS记录号	WOS:001361807400001
出版者	SPRINGERNATURE
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/458333
专题	生命科学与技术学院生命科学与技术学院_PI研究组_胡霁组
通讯作者	Xu, Xufeng; Zhang, Xia
作者单位	1.Sichuan Univ, West China Hosp, Mental Hlth Ctr, Chengdu, Peoples R China 2.Sichuan Univ, Inst Brain Funct & Dis, West China Hosp, Chengdu, Peoples R China 3.Chinese Inst Brain Res CIBR, Beijing, Peoples R China 4.Qingdao Univ, Affiliated Hosp, Neuropsychiat Res Inst, Qingdao, Peoples R China 5.Wenzhou Med Univ, Sch Optometry & Ophthalmol, Mol Neuropharmacol Lab, Wenzhou, Peoples R China 6.Wenzhou Med Univ, Eye Hosp, Wenzhou, Peoples R China 7.Peking Univ, Sch Life Sci, State Key Lab Membrane Biol, Beijing, Peoples R China 8.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 9.Fourth Mil Med Univ, Sch Basic Med, Dept Neurobiol, Xian, Peoples R China 10.Qingdao Univ, Sch Basic Med, Qingdao, Peoples R China
推荐引用方式 GB/T 7714	Tu, Zhaoyuan,Ma, Yao,Shang, Huiping,et al. Endocannabinoid interference blocks post-global cerebral ischemia depression through prefrontal cortico-amygdala projections[J]. NEUROPSYCHOPHARMACOLOGY,2024.
APA	Tu, Zhaoyuan.,Ma, Yao.,Shang, Huiping.,Zhao, Sha.,Xue, Bao.,...&Zhang, Xia.(2024).Endocannabinoid interference blocks post-global cerebral ischemia depression through prefrontal cortico-amygdala projections.NEUROPSYCHOPHARMACOLOGY.
MLA	Tu, Zhaoyuan,et al."Endocannabinoid interference blocks post-global cerebral ischemia depression through prefrontal cortico-amygdala projections".NEUROPSYCHOPHARMACOLOGY (2024).